Selenium and other trace elements in the etiology of Parkinson’s disease: a systematic review and meta-analysis of case-control studies

.INTRODUCTION Parkinson’s disease (PD) is a neurodegenerative illness recognised as the most common neurological disorder after Alzheimer’s dementia. Whereas the exact PD etiology remains unknown, risk of developing PD seems to be related to an interrelation of genetic and environmental factors, including also altered exposure to trace elements. In this systematic review and meta-analysis, we updated and summarized the results of epidemiologic case-control studies comparing levels of selenium, copper, iron and zinc in PD patients with healthy subjects in either blood (as whole blood, serum or plasma) and cerebrospinal fluid (CSF). MATERIALS AND METHODS We performed a systematic PubMed search and we included in our assessment only studies reporting demographic and disease-related characteristics, as well as trace element levels in different specimens (whole blood, serum/plasma and CSF). We then performed a meta-analysis of mean differences of trace element levels between cases and controls, using a random-effect model computing the weighted mean differences (WMD) and corresponding 95% confidence intervals (CI) to assess the association between serum/plasma, whole blood, CSF and selenium, copper, iron and zinc with Parkinson’s disease. RESULTS We retrieved 55 papers reporting data for selenium (588 cases and 721 controls), copper (2190 and 2522), iron (2843 and 3434), and zinc (1798 and 1913). Cases showed higher levels of selenium in CSF compared with controls (WMD=5.49; 95%CI 2.82 to 8.15), while levels in serum were similar (WMD=-0.22; -8.05 to 7.62). For copper cases showed higher levels in CSF and lower in serum compared to controls (WMD=1.87; -3.59 to 7.33, and -42.79, -134.35 to 48.76 respectively). Same results were found for iron in CSF (WMD=6.54; -1.97 to 15.04) and in serum/plasma (WMD=-58.19; -106.49 to -9.89 and whole blood (WMD=-95.69; 157.73 to -33.65). On the converse, cases had lower levels of zinc both in CSF (WMD=-7.34; -14.82 to 0.14) and serum/plasma (WMD=-79.93; -143.80 to -16.06). CONCLUSIONS Results of this systematic review and meta-analysis suggests that overexposure to environmental selenium, copper and iron may be risk factors for PD onset or progression. Alternatively, some variation in levels of these trace elements may occur as a consequence of the disease. Considering the burden of PD in the world population, further investigation of trace element exposure in this disease is therefore warranted, especially to plan possible prevention measures.